Osteoporosis is a systemic skeletal disease, characterised by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious consequence of osteoporosis, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated. The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the ageing of the population. World-wide fracture incidence is forecasted to increase three-fold over the next 60 years, and one study estimated that there will be 4.5 million hip fractures world-wide in 2050. Women are at greater risk of osteoporosis than men. Women experience a sharp acceleration of bone loss during the five years following menopause. Other factors that increase the risk include smoking, alcohol abuse, a sedentary lifestyle and low calcium intake. There are currently two main types of pharmaceutical therapy for the treatment of osteoporosis. The first is the use of anti-resorptive compounds to reduce the resorption of bone tissue. Estrogen is an example of an anti-resorptive agent. It is known that estrogen reduces fractures. In addition, Black, et al. in EP 0605193A1 report that estrogen, particularly when taken orally, lowers plasma levels of LDL and raises those of the beneficial high density lipoproteins (HDL's). However, estrogen failed to restore bone back to young adult levels in the established osteoporotic skeleton. Furthermore, long-term estrogen therapy, however, has been implicated in a variety of disorders, including an increase in the risk of uterine cancer, endometrial cancer and possibly breast cancer, causing many women to avoid this treatment. The significant undesirable effects associated with estrogen therapy support the need to develop alternative therapies for osteoporosis that have the desirable effect on serum LDL but do not cause undesirable effects. A second type of pharmaceutical therapy for the treatment of osteoporosis is the use of anabolic agents to promote bone formation and increase bone mass. Although there are a variety of osteoporosis therapies there is a continuing need and a continuing search in this field of art for alternative osteoporosis therapies. In addition, there is a need for bone fracture healing therapies. Also, there is a need for therapy, which can promote bone re-growth into skeletal areas where defects exist such as defects caused or produced by, for example, tumors in bone. Further, there is a need for a safer therapy with fewer side effects. In the art several studies have focussed on mechanisms of osteoclast activation. For example Niida et al (1999) have shown that vascular endothelial growth factor (VEGF) has a positive activity on osteoclast recruitment. One interesting homologue of VEGF is Placental growth factor (PIGF) but its role in bone has been poorly studied (Persico M. G. et al., 1999, Curr Top Microbiol Immunol 237, 31-40). U.S. Pat. No. 5,919,899 describes PIGF and its use in the treatment of inflammatory disorders, wounds and ulcers. Several inhibitors for PIGF signalling, such as antibodies and tetrameric peptides, are known in the art and are disclosed in WO 01/85796, while also Carmeliet et al Nature medicine May 2001 Volume 7 Number 5 pp 575-583 discloses neutralising anti-PLGF antibodies.
The present invention relates to the finding that antagonists of PIGF can be used for the manufacture of a medicament to suppress disorders of bone resorption such as osteoporosis.